TRAIL受体在人肝细胞癌中的表达及TRAIL诱导的肝癌细胞凋亡

目的 研究了RAIL受体在肝癌组织及肝癌细胞中的表达,探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其受体在肝癌细胞凋亡诱导中的作用。 方法 应用RT-PCR法和免疫组化方法检测肝癌组织及细胞系SK-Hepl中TRAIL受体的表达,并以TRAIL蛋白和γ-干扰素作用于SK-Hepl细胞,观察其对细胞的凋亡诱导作用。 结果 在肝癌组织及肝癌SK-Hepl细胞系中均可检测到TRAIL受体,其中,死亡受体DR4、DR5在肝癌、癌旁组织以及SK-Hepl肝癌细胞系中均呈高表达,而诱骗受体DcR1及DcR2呈低表达,明显低于正常组织。TRAIL对肝癌细胞有凋亡诱导作用,与干扰素的协同时,其作用明显增强。 结论 肝癌组织中存在着TRAIL受体的表达,TRAIL可诱导肝癌SK-Hepl细胞系凋亡,其作用与DR4、DR5的高表达有关。

Expression of TRAIL receptors in human hepatocellular carcinoma and apoptosis induced by TRAIL

Objective: To investigate the expression of TRAIL receptors in human hepatocellular carcinoma and neighboring non-tumor liver tissues and to study its roles in apoptosis of SK-Hep1 cell line.Methods: The expression of TRAIL receptors in hepatocellular carcinoma and in SK-Hep1 cell line was detected by immunohistochemical staining and RT-PCR, and the apoptosis of SK-Hep1 cell line induced by recombinant human TRAIL together with or without INF-γ was measured by FCM.Results: The expression of four TRAIL receptors was detectable in human hepatocellular carcinoma and neighboring non-tumor liver tissues. High expression of DR4 and DR5 was detected in tumor and neighboring non-tumor liver tissues whereas low expression of DcR1 and DcR2 was found in tumor, significantly lower than that in normal liver tissues (67.86% vs 100%, 78.57% vs 100%, respectively,P<0.01. TRAIL together with INF-γ strongly increased the apoptosis of SK Hep1 cell line.Conclusion: The four TRAIL receptors can be detected in hepatocellular carcinoma and in SK-Hep1 cell line. Combinations of TRAIL and INF-γ may be a useful alternative to HCC. This project was supported by Chinese National Natural Science Foundation, and the Dawn Foundation of Shanghai Educational Committee.